APPLICANT'S ABSTRACT: This is an application in response to RFA AA-94-06, Medications Development for Alcohol-Related Problems. Alcohol abuse continues to present a significant problem from a health-care perspective and the development of safe and effective pharmacotherapies that will not interact with other medications remain a major priority. We propose to conduct a clinical study using a non toxic food product, kudzu. The root of this leguminous plant, Radix puerariae, contains two isoflavones, daidzin and daidzein, that have been shown to reduce ethanol intake by hamsters and attenuate ethanol's effects in rats and mice; a kudzu preparation decreased many of ethanol's subjective, performance and physiologic effects in women but not men in our pilot study. The proposed study will be conducted to explore the pharmacodynamic effects of a two-day isoflavone treatment regimen on the acute ethanol response in occasional drinkers. Compliance will be determined by measuring plasma daidzein levels and urinary riboflavin levels which will be added to all doses. Dependent measures include physiological date (heart rate, blood pressure, skin temperature), subjective levels of intoxication and responses to standardized behavioral instruments including (Visual Analog Scales (VAS), Subjective High Assessment Scale (SHAS), Profile of Mood States (POMS) and psychomotor performance (stance stability, Digit Symbol substitution Test (DSST) and continuous performance reaction times). Frequent blood samples will be withdrawn and analyzed for plasma ethanol and acetaldehyde levels to determine if isoflavones alter ethanol absorption or elimination pharmacokinetics. This double-blind and placebo-controlled study will be conducted to measure the effects of two dose levels of isoflavones on two doses of ethanol in adult males and females. Women will be studied during both the follicular and luteal phase of the menstrual cycle. Data obtained from these studies will enhance our basic understanding of the nature of the interactions between isoflavones and ethanol and how this relationship may alter ethanol's intoxicating and reinforcing effects. If isoflavone treatment proves to attenuate ethanol's effects, then it may be useful as an effective pharmacotherapy for alcoholism. If so, then health-care providers will have a new non toxic medication/food product to offer their patients to help curb their ethanol intake. Because of its low toxicity, isoflavone preparations may be made available to a wider population including those who are currently problem drinkers and have not yet been diagnosed as alcohol dependent.